caga

cagA is a gene in Helicobacter pylori encoding the cytotoxin-associated antigen A protein, a major virulence factor. It is located within the cag pathogenicity island (cag PAI) of many virulent strains, a genomic region that encodes a Type IV secretion system and regulatory proteins.

During infection, CagA is translocated into gastric epithelial cells by the bacterial Type IV secretion system. Once inside, CagA can be phosphorylated on tyrosine residues within conserved EPIYA motifs by host kinases such as Src. Phosphorylated CagA binds the SHP-2 phosphatase, activating downstream signaling pathways including the MAPK/ERK cascade, promoting changes in cell morphology and proliferation. CagA can also interact with other host factors, disrupting tight junctions and cell polarity, and enhancing inflammatory responses, including interleukin-8 production.

Cellular effects include the hummingbird phenotype (elongated, spindle-like cells) and disruption of adherens and tight junction proteins, contributing to gastric mucosal damage and barrier dysfunction.

Clinical significance: Infection with cagA-positive H. pylori is associated with a higher risk of peptic ulcer disease and gastric adenocarcinoma compared with cagA-negative strains. The oncogenic potential varies with EPIYA motif composition: East Asian strains with EPIYA-D segments tend to have stronger SHP-2 interaction and higher cancer risk than Western strains with EPIYA-C.

Genetic variability and evolution: The cag PAI is absent in many strains, but when present it is associated with enhanced virulence. Epidemiology varies geographically, and cagA prevalence correlates with disease risk in certain populations. Detection of cagA can support assessment of virulence potential in H. pylori infections.